CN116966138B - Application of gel in preparation of medicine for improving AMH value - Google Patents
Application of gel in preparation of medicine for improving AMH value Download PDFInfo
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- CN116966138B CN116966138B CN202311226689.5A CN202311226689A CN116966138B CN 116966138 B CN116966138 B CN 116966138B CN 202311226689 A CN202311226689 A CN 202311226689A CN 116966138 B CN116966138 B CN 116966138B
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Classifications
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Abstract
The invention belongs to the technical field of treatment of reduction of ovarian reserve function, and particularly discloses application of gel in preparation of a medicine for improving an AMH value. The small molecular ovarian cell nutrients in the gel restore the ovarian function and improve the ovarian reserve function through repairing and nourishing the ovarian cells, the increase of the AMH concentration in serum is shown, and for women of child-bearing age with lower AMH values, the AMH values are improved to different degrees, so that the gel has great application prospect in improving the ovarian function and the reserve function of women, and has wide market application.
Description
Technical Field
The invention relates to the technical field of treatment of ovarian reserve function decline, in particular to application of gel in preparation of a medicine for improving an AMH value.
Background
Hypoovarianism refers to the process by which the ovaries gradually lose their normal function within a particular age group of females, usually after the age of 40. This includes a reduced number of oocytes in the ovary, a reduced quality and a reduced hormone secretion capacity. Wherein reduced number and reduced quality of oocytes in the ovary are manifestations of reduced ovarian reserve function (DOR), also known as reduced ovarian reserve function. Clinically, it is manifested by hypomenorrhea, menstrual disorder, amenorrhea, difficult pregnancy, and climacteric symptoms. Anti-mullerian hormone (anti-Mullerian hormone, AMH), a hormone produced in follicles that is positively correlated with the number of follicles, is generally considered to be one of the indicators reflecting ovarian reserve function. Thus, a decrease in AMH levels is an indicator of decreased ovarian reserve.
Compared with other traditional biological indexes, AMH is not regulated by hypothalamus-pituitary-ovary axis, is basically constant in menstrual cycle, and is the most accurate biomarker for evaluating the aging degree of ovary and the function of ovary reserve. For example, chinese patent application CN115297929a discloses a composition and method for modulating folliculogenesis for the treatment of ovarian aging, providing a method and composition related to modified proteins of anti-mullerian hormone (AMH) for modulating folliculogenesis in females, in particular for modulating activation and maturation of follicles and depletion of immature (primordial) follicles. For example, chinese patent application CN113368190a discloses a traditional Chinese medicine composition for treating ovarian hypofunction, which is prepared from active ingredients and pharmaceutical excipients, wherein the active ingredients comprise: 5-30 parts of stir-fried bighead atractylodes rhizome, 8-25 parts of prepared rehmannia root, 10-40 parts of prepared rhizoma polygonati, 5-20 parts of stir-fried white paeony root, 10-40 parts of suberect spatholobus stem, 3-12 parts of tortoise plastron, 3-12 parts of deer horn slices, 5-25 parts of red sage root, 3-12 parts of eucommia ulmoides, 8-25 parts of codonopsis pilosula, 3-12 parts of prepared nutgrass galingale rhizome and 3-12 parts of bitter orange, and the traditional Chinese medicine composition can obviously relieve the menstrual flow reduction symptoms related to hypoovarium and has an adjusting effect on the related hormone AMH reflecting the reduction of the ovarian reserve function. However, the traditional Chinese medicine composition is unsuitable for external use and has relatively poor treatment effect due to small amount of active efficacy components and large molecular weight.
There is a need for an external product that can improve the decline of ovarian reserve and significantly increase the AMH value.
Disclosure of Invention
In order to solve the technical problems, the invention provides application of gel in preparing a medicament for improving an AMH value, wherein the gel adopts a composite plant fermentation concentrated solution as an active component, the composite plant fermentation concentrated solution contains micromolecular ovarian cell nutrients obtained by fermenting composite plant raw materials and also contains lactobacillus fermentation lysate, and the gel can help to repair the ovarian function of females with hypoovariance and hypoovariance, thereby improving the hypoovariance and reflecting that the AMH concentration in serum is improved.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
the invention provides application of gel in preparation of a medicine for improving an AMH value.
Preferably, the gel comprises the following components in parts by weight: 10-70 parts of composite plant fermentation concentrated solution, 0.2-2 parts of silver-containing bacteriostat, 5-30 parts of surfactant, 1-10 parts of auxiliary materials, 10-50 parts of purified water and 2-10 parts of glycerol; the composite plant fermentation concentrated solution is prepared by taking radix puerariae extract, rhizoma polygonati extract, ampelopsis grossedentata extract, alpinia oxyphylla extract and clove extract as composite plant raw materials, and fermenting the composite plant raw materials by using composite lactobacillus to obtain secondary metabolites; the composite lactobacillus comprises lactobacillus plantarum, lactobacillus casei and lactobacillus acidophilus.
Preferably, the composite plant fermentation concentrated solution is prepared from the following raw materials in parts by weight: 80-90 parts of purified water, 4.5-8.0 parts of radix puerariae extract, 1.3-3.5 parts of rhizoma polygonati extract, 0.7-2.4 parts of ampelopsis grossedentata extract, 0.7-2.2 parts of fructus alpiniae oxyphyllae extract, 0.4-1.3 parts of clove extract and 3.5-7.5 parts of lactobacillus compoundus.
Preferably, the preparation process of the composite plant fermentation concentrate comprises the following steps: mixing radix Puerariae extract, rhizoma Polygonati extract, ampelopsis grossedentata extract, fructus Alpinae Oxyphyllae extract, flos Caryophylli extract and water, adjusting pH to 2-7, adding lactobacillus after propagation, fermenting, concentrating to relative density of 0.9-1.2 at 20deg.C, centrifuging, and sterilizing.
Preferably, the fermentation conditions are 35-39deg.C for 5-8 days.
Preferably, the centrifugation conditions are 3000-5000r/min for 10-30min.
Preferably, the Silver-containing bacteriostat is selected from at least one of Jetel Silver II, procare ESI, AC1000-D and HYMAg-M.
Preferably, the surfactant is selected from one or more of poloxamer 407, poloxamer 188, tween 80, span 80, AES, AOS, AEO-7, cocodiethanolamide and cocoamidopropyl betaine.
Preferably, the purified water is selected from distilled water and/or deionized water; the auxiliary material is at least one selected from 1, 2-hexanediol, 1, 2-pentanediol and isopentyl glycol.
Preferably, the preparation method of the gel comprises the following steps:
s1, adding purified water into a stirring pot, stirring and heating to 70-95 ℃, and preserving heat for 20-40min;
s2, weighing the composite plant fermentation concentrated solution and auxiliary materials, and uniformly stirring to obtain a mixture;
s3, adding the mixture obtained in the step S2 and the silver-containing bacteriostat into the stirring pot obtained in the step S1, and stirring until the mixture is uniform;
s4, adding a surfactant under stirring, maintaining the temperature, and soaking for 1-3 hours; stirring until the mixture is dissolved and completely transparent after the soaking is completed;
s5, adding glycerol for several times under stirring, and stirring until the mixture is uniform;
s6, filtering, discharging, sealing, standing, checking, filling, packaging and warehousing after the spot inspection is qualified.
Preferably, the stirring speed in the step S1 is 10-20 revolutions per minute; the stirring speed of adding the surfactant under stirring in the step S4 and the stirring speed after soaking is 5-10 rpm, and the stirring speed in the step S5 is 20-30 rpm.
Preferably, the therapeutic disease of the medicament includes hypofunction of ovarian reserve, polycystic ovary syndrome, ovarian inflammation and premature ovarian failure.
Preferably, the route of administration of the drug is via the luminal route.
In particular, the route of administration of the drug is vaginal.
The beneficial effects of the invention are as follows:
the invention provides an application of gel in preparing a medicament for improving an AMH value, and micromolecular ovarian cell nutrients in the gel are used for restoring ovarian function and improving the hypofunction of ovarian reserve through repairing and nourishing ovarian cells, wherein the increase of the AMH concentration in serum is shown. For women of child bearing age with lower AMH value, the AMH value is improved to different degrees after the gel provided by the invention is used, which reflects the great application prospect of the gel product in improving female ovary function and reserve function, and has wide market application.
Drawings
FIG. 1 is a graph showing the relationship between AMH content and age before administration in Experimental example 2 of the present invention;
FIG. 2 is a graph showing the relationship between AMH content and age after administration in Experimental example 2 of the present invention;
FIG. 3 is a graph showing the relationship between AMH increment and age before and after administration in Experimental example 2 of the present invention;
FIG. 4 is a graph showing the relationship between AMH growth rate and age before and after administration in Experimental example 2 of the present invention;
FIG. 5 is a graph showing the relationship between AMH content and BMI before administration in experimental example 3 of the present invention;
FIG. 6 is a graph showing the relationship between AMH content and BMI after administration in experimental example 3 of the present invention;
FIG. 7 is a graph showing the relationship between AMH increment and BMI before and after administration in experimental example 3 of the present invention;
FIG. 8 is a graph showing the relationship between AMH growth rate and BMI before and after administration in experimental example 3 of the present invention;
FIG. 9 is a graph showing the relationship between the average value and median AMH content increase before and after administration in experimental example 2 of the present invention, wherein a is the average value and b is the median.
Detailed Description
The following examples are presented only to aid in understanding the method of the present invention and its core ideas. It should be noted that it will be apparent to those skilled in the art that various modifications and adaptations of the invention can be made without departing from the principles of the invention and these modifications and adaptations are intended to be within the scope of the invention as defined in the following claims. The following description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described herein.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
The following raw material sources are exemplary illustrations:
radix Puerariae extract: KUDZU ROOT p.e. from the biotechnology company, inc;
rhizoma Polygonati extract: polygonatuM officinale, ext, from biotechnology, inc;
ampelopsis grossedentata extract: ampelopsis grossedentata (AMPELOPSIS GROSSEDENTATA) extract from Huzhou Pu Rui biomedical technologies Co., ltd;
an extract of alpinia oxyphylla: purchased from Hunan Langlin biological resource Co., ltd;
flos Caryophylli extract: purchased from Shaanxi pannier Biotech Co., ltd;
silver-containing bacteriostat: jetel Silver II, available from Haen Biotechnology, inc., germany;
and (2) a surfactant: poloxamer 407, commercially available;
lactic acid bacillus: lactobacillus plantarum NDC75017 (viable count 2.0X10) 10 CFU/g), lactobacillus acidophilus NCFM (viable count 2.0X10) 10 CFU/g), the important laboratory preservation strain of the northeast agricultural university dairy science education department; lactobacillus casei NCU011056 (viable count 2.0X10) 10 CFU/g), the strain is deposited in the national emphasis laboratory of the university of south China, the food science and the technology;
pH regulator: citric acid, commercially available;
auxiliary materials: 1, 2-hexanediol, commercially available;
glycerol, deionized water: are commercially available.
Example 1
1. Preparation of composite plant fermentation concentrate
(1) Preparation of a culture medium: adding 6 parts of radix puerariae extract, 2 parts of rhizoma polygonati extract, 1.6 parts of ampelopsis grossedentata extract, 1.6 parts of fructus alpiniae oxyphyllae extract, 0.8 part of clove extract and 84 parts of water into a triangular flask, regulating the pH to 3.5 by using citric acid, uniformly mixing, adding a cotton plug into a bottle mouth, wrapping newspaper, sterilizing for 20min in a portable autoclave at 115 ℃, and taking out as a liquid culture medium for standby.
(2) And (3) strain expansion culture: under the aseptic condition, respectively picking a loop of lactobacillus plantarum, lactobacillus casei and lactobacillus acidophilus by using an inoculating loop, transferring into different sterilized test tubes, drawing a curve, culturing in a horizontal test tube at 32 ℃ for 7 days, transferring again under the same operation condition after the colony grows, and culturing conditions are the same as above. The strain is used for experiments after 3 generations of activation process.
(3) Fermentation: the selected culture temperature is 35 ℃ +/-1 ℃, sterile water is added into an activated inclined surface test tube, spores are eluted, a sterilization pipette is used for sucking spore suspension, 4% of inoculation amount (the mass ratio of lactobacillus plantarum to lactobacillus casei to lactobacillus acidophilus is 1:1.5:1.5) is transferred into a standby liquid culture medium, shake culture is carried out, the rotation speed is 120 r/min, the culture temperature is 35 ℃, and the culture fermentation is carried out for 7 days. Concentrating the fermentation broth to relative density of 1.05 at 20deg.C, centrifuging at 4000r/min for 20min, and sterilizing.
2. Preparation of gels
The specific formulation is shown in Table 1. The preparation process comprises the following steps:
1) Adding purified water into a stirring pot, stirring at 20 rpm, heating to 85deg.C, and maintaining the temperature for 30min;
2) Weighing the composite plant fermentation concentrated solution and auxiliary materials in a sterilized and dried container, and uniformly stirring;
3) And (3) keeping the materials in the stirring pot in the step (1) completely warm, keeping stirring, and starting cooling water for cooling. Cooling to 30 ℃, adding the mixture obtained in the step 2) and the silver-containing bacteriostat, and stirring until the mixture is uniform;
4) Adding surfactant under slow stirring (10 rpm), maintaining the temperature, and soaking for 2 hr; after the soaking is completed, stirring for 10 revolutions per minute until the mixture is dissolved and completely transparent;
5) Slowly adding glycerol for three times under 30 r/min stirring, and stirring to uniformity;
6) And after the sampling inspection is qualified, filtering and discharging, sealing and standing, inspecting, filling, packaging and warehousing.
Comparative example 1
1. Preparation of composite plant fermentation concentrate
(1) Preparation of a culture medium: adding 8 parts of radix puerariae extract, 4 parts of rhizoma polygonati extract and 84 parts of water into a triangular flask, regulating the pH to 3.5 with citric acid, mixing uniformly, adding a cotton plug into a bottle mouth, wrapping newspaper, sterilizing in a portable autoclave at 115 ℃ for 20min, and taking out for later use.
(2) And (3) strain expansion culture: as in example 1.
(3) Fermentation: as in example 1.
2. Preparation of gels
The specific formulation is shown in Table 1. The preparation process is the same as in example 1.
Table 1 gel formulations of examples and comparative examples
Comparative example 2
Mixing radix Puerariae extract 6 parts, rhizoma Polygonati extract 2 parts, ampelopsis grossedentata extract 1.6 parts, fructus Alpinae Oxyphyllae extract 1.6 parts, flos Caryophylli extract 0.8 parts and water 84 parts to obtain the final product.
Experimental example 1 Effect of gel on DOR rats
1. Modeling: after 12 week old female SD rats were acclimatized for one week, all rats were observed for vaginal abscission cells using Rayleigh-Giemsa (Wright-Giemsa) complex dye solution at two consecutive daily intervals. Sucking 0.9% sodium chloride solution by using a 20 mu L pipettor, slowly inserting the solution into the vagina of a rat for about 0.3cm, repeatedly sucking the solution for 3 times, uniformly transferring the liquid containing the exfoliated cells in the pipette tip onto a glass slide, performing cell staining observation according to Wright-Giemsa instruction operation, screening out rats with normal estrus cycle, randomly selecting 10 rats into a normal group, taking the rest rats into the normal group, adopting a 75mg/kg induction DOR model method of disposable intraperitoneal Cyclophosphamide (CTX), taking all rats to be fasted for about 12 hours before molding, preparing 0.2g CTX by using 10mL of 0.9% sodium chloride solution, placing the prepared solution in a refrigerator at 4 ℃ and injecting the solution in 2 hours, selecting the lower abdomen of the rat at the left side of the rat, simultaneously placing the rat in the lower head position, injecting the rat into the abdominal cavity at an angle of 45 DEG with the abdominal cavity wall, avoiding puncturing the bladder and the abdominal cavity, sucking the rest rats into the abdominal cavity for about 0.5cm, slowly injecting the medicament into the thumb, and ensuring that the medicament is gently distributed by pushing the thumb of the rats. Normal group rats are injected with the same dosage of 0.9% sodium chloride solution, then the normal estrus cycle of the rats is 4-5d by observing the vaginal abscission cytology of the rats of the modeling group at daily time for two weeks, and if the estrus cycle is disordered, the estrus cycle is prolonged to be mainly expressed, so that modeling success is indicated.
2. Grouping and medication: the rats successfully molded were randomly divided into 10 groups of a model group, a example 1 group, a comparative example 1 and a comparative example 2, and the example 1 group and the comparative example 1 group were slowly inserted into the vagina of the rat to be administered by 0.3g/kg of the gel of the example 1 and the comparative example 1, respectively, for about 0.3 cm; comparative example 2 group lavage the composition of comparative example 2 was 0.8g/kg; the normal group and the model group were administered with the same dose of sodium chloride solution, each group was administered once daily, and after 3 weeks of administration, intraperitoneal injection was performed at a dose of 10% chloral hydrate (0.6 ml/dose), abdominal aortic blood collection was performed under anesthesia, standing at room temperature for 1 hour, centrifugation was performed at 3000r/min for 10min, and then serum was taken out and left standing for use. AMH was detected using a rat AMH ELISA kit (Shanghai Emblica Biotechnology Co., ltd., cat. No. CB 10627-Ra) and was operated strictly according to the instructions of the kit.
3. Experimental results: compared with the normal group, the AMH value of the model group is obviously reduced; the examples can significantly increase the value of AMH compared to the model group, whereas the comparative examples can increase the AMH content but the effect is not significant. The gel of the invention is shown to be capable of significantly increasing the AMH value. The specific results are shown in Table 2.
TABLE 2 influence of groups on DOR rat AMH
Note that: compared with the normal group, # represents P<0.01, compared with the model group,represents P<0.01。
Experimental example 2 Effect of gel on AMH values of samples of different ages
Volunteer selection criteria: female volunteers with special attention to self-ovary health are firstly subjected to a round of form filling screening, and the volunteers which trigger any one of the four items of natural infertility, irregular menstruation, sexual desire decline, hot flashes and sweating are selected into a desired list. It was then determined that the ovarian function was relatively low and that the corresponding basal AMH values may also be relatively low to schedule for physical examination.
The experimental method comprises the following steps: 43 volunteers (30-50 years) were selected to meet the requirements and the product was pushed directly into the vagina using the gel of example 1. 2.5 g of 1 pill, 1 pill per day during non-menstrual period, and 21 days continuously. The AMH value is detected. The trend of AMH increase with age in 43 volunteers was analyzed using pearson correlation: of these, 30-44 years (32) volunteers were more concentrated, and age stratification analysis was performed at ages 30-34, 35-39 and 40-44, with specific results shown in Table 3 and FIGS. 1-4. The average and median AMH growth of pre-and post-drug volunteers were analyzed using t-test and wilcox test, respectively (specific calculation method is that before using gel, the AMH values of 43 volunteers were averaged as the average before drug use, sorted by AMH value size, the AMH values of 22 volunteers were as the median before drug use, after using gel, the AMH values of 43 volunteers were averaged as the average after drug use, sorted by AMH value size, the AMH values of 22 volunteers were as the median after drug use). And the user who had increased AMH after using the gel was defined as effective, and the effective rate and the increase rate of the medication were analyzed, and the specific results are shown in tables 4 to 5 and fig. 9.
In fig. 1-9, R represents a correlation coefficient, which is an amount of linear correlation between study variables, and when the value is a positive value, it represents a positive correlation between two random variables; when the value is a negative value, the two random variables are represented to be in a negative correlation relationship; when the value is 0, the linearity between the two random variables is irrelevant; p is used for judging the consistency between the actual observation result and the original assumption, if the P value is smaller (usually smaller than 0.05), the observation result is not consistent with the original assumption, and the original assumption can be refused, wherein the original assumption is that the AMH value is unchanged after the product of the invention is used, and the assumption is overturned based on the P value being smaller than 0.05, so that the AMH value is obviously changed before and after the product of the invention is used.
TABLE 3 effective and growth rate ratios of gels for different age groups
As can be seen from the results of table 3, there is no significant difference in effective rate between users of different ages, and there is comparability.
TABLE 4 growth rate of mean and median before and after gel use
From a comparison of the results in table 4 and fig. 9, the average value of AMH increases by about 43% and the median value increases by about 83% in 43 volunteers after the gel is used, compared with before the gel is used, indicating that the AMH value can be significantly increased after the gel of the present invention is used.
TABLE 5 effective conditions before and after gel application
As can be seen from table 5, the total effective user ratio after the gel was used was 72%, significantly higher than 50%.
From the results of fig. 1 and 2, it can be seen that, whether gel is used or not, the AMH value gradually decreases with age to about 50 years old, and the AMH value decreases to near 0, which also objectively reflects the rule that the ovarian reserve function decreases with age.
As can be seen from fig. 3, after using 21 gels, the AMH increase value was different at different ages, and the increase value tended to decrease with age. This means that the earlier the adjustment, the higher the AMH increase value.
As can be seen from fig. 4, after using 21 gels, the AMH increase value decreased with age, but the AMH increase rate tended to increase with age. This means that, for older people, the AMH increase value is relatively low, but the AMH increase rate is increased due to the lower cardinality.
Experimental example 3 Effect of gel on AMH values of different BMI samples
The experimental method comprises the following steps: 43 volunteers in experimental example 2 were selected, BMI values were calculated as "BMI=body weight kg/(height cm/100)/(2)", the trend of AMH values and BMI changes before and after use was analyzed using pearson correlation, BMI was grouped as "BMI <20" was too light, "20-25" was normal, "25" was too heavy, and the gel of example 1 was used to push the product directly into the vagina. 2.5 g of 1 pill, 1 pill per day during non-menstrual period, and 21 days continuously. AMH values are detected, and the relation between AMH change values and BMI is compared.
The specific results are shown in fig. 5-8.
From fig. 5, 6 and 7, it can be seen that the three indexes of the AMH value before the gel, the AMH value after the gel and the AMH growth difference value do not change significantly with the BMI (the P values are all greater than 0.05). This indicates that the AMH value is not highly correlated with BMI; there was no significant difference in AMH increase values for different BMI populations using gel dry prognosis.
As can be seen from fig. 8, the AMH growth rate increased significantly with the increase of BMI after the gel was used, demonstrating that the gel of the present invention has a good effect on the growth of patients with a larger BMI index.
The invention has been further described with reference to specific embodiments, which are exemplary only and do not limit the scope of the invention in any way. It will be understood by those skilled in the art that various changes and substitutions of details and forms of the technical solution of the present invention may be made without departing from the spirit and scope of the present invention, but these changes and substitutions fall within the scope of the present invention.
Claims (3)
1. The application of the gel in the preparation of the medicines for improving the AMH value is characterized in that the gel comprises the following components in parts by weight: 42.6 parts of composite plant fermentation concentrated solution, 0.6 part of silver-containing bacteriostat, 18 parts of surfactant, 1.4 parts of auxiliary materials, 31.4 parts of purified water and 6 parts of glycerol; the composite plant fermentation concentrated solution is prepared from the following raw materials in parts by weight: 84 parts of purified water, 6 parts of kudzuvine root extract, 2 parts of rhizoma polygonati extract, 1.6 parts of ampelopsis grossedentata extract, 1.6 parts of sharpleaf galangal fruit extract, 0.8 part of clove extract and 3.84 parts of lactobacillus complex;
the preparation method of the gel comprises the following steps:
s1, adding purified water into a stirring pot, stirring and heating to 85 ℃, and preserving heat for 30min;
s2, weighing the composite plant fermentation concentrated solution and auxiliary materials, and uniformly stirring to obtain a mixture;
s3, adding the mixture obtained in the step S2 and the silver-containing bacteriostat into the stirring pot obtained in the step S1, and stirring until the mixture is uniform;
s4, adding a surfactant under stirring, maintaining the temperature, and soaking for 2 hours; stirring until the mixture is dissolved and completely transparent after the soaking is completed;
s5, adding glycerol for several times under stirring, and stirring until the mixture is uniform;
s6, filtering and discharging after the spot inspection is qualified, sealing and standing, checking, filling, packaging and warehousing;
the composite plant fermentation concentrated solution is prepared by taking radix puerariae extract, rhizoma polygonati extract, ampelopsis grossedentata extract, alpinia oxyphylla extract and clove extract as composite plant raw materials, and fermenting the composite plant raw materials by using composite lactobacillus to obtain secondary metabolites; the composite lactobacillus is lactobacillus plantarum, lactobacillus casei and lactobacillus acidophilus, and the mass ratio is 1:1.5:1.5;
the Silver-containing antibacterial agent is Jetel Silver II; the surfactant is poloxamer 407; the purified water is deionized water; the auxiliary material is 1, 2-hexanediol.
2. The use according to claim 1, wherein the therapeutic condition of the medicament comprises at least one of reduced ovarian reserve, ovarian inflammation and premature ovarian failure.
3. The use according to claim 1, wherein the route of administration of the medicament is via the luminal route.
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